Kent E. Wika

A comprehensive hematologic study in calves with total artificial hearts.

Thromboembolism and infection remain potential threats for long-term circulatory assist and replacement devices. The alteration of the hemostatic system and of blood cell functions caused by device implantation may predispose the recipient to these complications. Many sensitive coagulation assays and the technology of flow cytometry would be powerful tools for this investigation. The availability of such immunologic technologies for animal species other than humans has yet to be established. In a series of in vitro tests we found that the following assays, among others, are usable in calves: TAT, TxB2, platelet surface glycoprotein IIbIIIa, and membrane aminophospholipid. F1.2, D-dimer, beta TG, PF-4, and platelet surface expression of GMP-140 and receptors for fibronectin, thrombospondin, and vWF were not measurable. A sustained mild decrease in hematocrit levels in six calves with the Cleveland Clinic-Nimbus total artificial heart for 11-120 days was attributed to an increase in circulating blood volume, but not to red blood cell damage. Whole blood platelet aggregation was suppressed only for the first 3 post operative days, with decreased GPIIbIIIa expression. Polymorphonuclear phagocytosis, chemotaxis, and superoxide anion production were not altered. Device infection and thromboembolism occurred in one of 13 cases overall.

Progress in Cleveland Clinic-Nimbus total artificial heart development

A totally implantable, Cleveland Clinic-Nimbus total artificial heart (TAH) uses electrohydraulic energy conversion and an automatic left master-alternate mode control scheme, with a filling sensitivity of 1.0 l/min/mmHg and a maximum output of 9.5 l/min. The TAHs were tested in 12 calves for 1-120 days with normal major organ and blood cell function. Post-operative suppression of platelet aggregation recovered by the second post-operative week. The gelatin-coated pump surface generally was clean without any anticoagulants and free from infection. Embolism, which occurred in two cases, was caused by complications attributable to fungal infection in a Dacron graft and by thrombus formed around a jugular vein catheter. A system with a hybridized microcircuit controller in the interventricular space has been tested successfully in the three most recent cases, with a peak device surface temperature elevation of 6.5 degrees C. Heat effects were confined to the tissues immediately adjacent to the hottest spots. The carbon fiber-reinforced epoxy housing and 60 ml butyl rubber compliance chamber showed good tissue compatibility with a thin, fibrous tissue capsule. The transcutaneous energy transmission system and the internal battery functioned well as designed in the most recent animal implant.

Platelets are deposited early post-operatively on the leaflet of a mechanical heart valve in sheep without post-operative anticoagulants or antiplatelet agents: A scanning electron microscopic observation of the pyrolytic carbon surface in a mechanical heart valve

Pyrolytic carbon has been used for mechanical heart valves as a thromboresistant, wear resistant, and fatigue resistant material. Thrombosis and thromboembolism, however, remain major mechanical heart valve associated complications and may frequently occur during the early post-operative period. In depth morphologic studies on blood-pyrolytic carbon surface interactions are limited. The purpose of this study was to evaluate the blood compatibility of the pyrolytic carbon surface of St. Jude Medical mechanical heart valves that were implanted in the mitral position of sheep without the administration of post-operative anticoagulants or antiplatelet agents for 2, 4, and 6 weeks. Almost the entire leaflet and orifice ring surfaces were observed by scanning electron microscopy. Although the surfaces appeared clean macroscopically, when observed by electron microscopy, the surface were mottled, mainly by solitary platelets and aggregations. There were only a few leukocytes or red blood cells observed. No fibrin clots were observed on the leaflets. The density of platelet deposition was higher in the vicinity of the pivots and near the edges of the leaflets. The sizes of the platelet aggregations decreased with longer duration. The outer surfaces of the pivot guards were covered by various amounts of deposition composed of platelet aggregations and thrombi. Thus, the administration of antiplatelet agents is recommended during the early post-operative period after mechanical heart valve implantation.

Blood compatibility of a newly developed trileaflet mechanical heart valve.

An ideal heart valve prosthesis, which has both the flow dynamic properties and blood compatibility of a tissue valve prosthesis and the durability of a mechanical prosthesis, does not exist. The Triflo trileaflet mechanical heart valve (MHV; Triflo Medical Inc., Irvine, CA) is a newly developed MHV prosthesis with the following design goals: central flow, minimal flow disturbance and stasis around the hinge region, and durability. The current study was conducted to evaluate the blood compatibility of a 29 mm Triflo MHV in the mitral position of eight calves for 5 months without any postoperative anticoagulation. Whole blood platelet aggregometry and the Xylum Clot Signature Analyzer (Xylum Corporation, Scarsdale, NY) were used to evaluate the postoperative changes in platelet and coagulation functions. Full autopsies, histological examinations of major internal organs, and scanning electron microscopy analyses of the explants were performed. Early termination occurred in two cases; one was because of valve thrombosis on the 25th day, and the other was killed because of a nonvalvular complication on the 105th day. The valve thrombosis was attributed to prolonged ventricular fibrillation at the time of valve replacement surgery. Whole blood platelet aggregometry and clot signature analyzer parameters did not show any sign of activation of platelets or the coagulation system. No hemolysis was observed. There was no macroscopic valve thrombosis or embolism observed in the remaining seven cases. Scanning electron microscopy analyses showed clean leaflet and valve ring surfaces, with only occasional minute platelet aggregations. Excellent blood compatibility of the Triflo MHV was demonstrated in this study.

Heat from an implanted power source is mainly dissipated by blood perfusion.

Heat dissipation and its effects on tissue and blood interfaces are common problems associated with the development and increased use of artificial hearts, because all of the implantable actuators for artificial hearts generate waste heat due to inefficiencies of energy conversion. To determine the mechanisms of heat dissipation from artificial hearts, heated disks producing constant heat fluxes of 0.08 watts/cm2 were implanted adjacent to the left lung and the latissimus dorsi muscle in calves for 2 weeks, 4 weeks, and 7 weeks. At the end of each experiment, a series of acute studies was performed in which blood perfusion to the heated tissue was decreased or stopped to observe the contribution of blood perfusion to heat dissipation. The cooling effect of ventilation was also examined to determine its relative contribution to heat dissipation in lung tissue by decreasing the minute ventilation volume. The importance of blood perfusion for heat dissipation was demonstrated by the temperature rise after cessation of blood perfusion to the heated tissue. The contribution of ventilation to heat dissipation in the heated lung tissue was minimal. Contribution of total blood perfusion to heat dissipation was increased with time in the muscle tissue, which has relatively low resting blood perfusion, but not in the lung tissue, which has relatively high blood perfusion. In the heated muscle tissue, the in vivo adaptive response to chronic heat was functionally shown by the increased perfusion. In conclusion, blood perfusion was the main mechanism of heat dissipation from tissues that were adjacent to an implanted power source. ASAIO Journal 1997; 43:M585-M588.

Assessment of circulating blood volume in calves with a total artificial heart

Measurement of the circulating blood volume (CBV) is essential to a proper understanding of the hemodynamic performance of total artificial hearts (TAHs). Recently, the authors employed CBV measurements using indocyanine green dye in calves with a TAH. The advantages of this method over previous methods using radionuclides include simplicity, low cost, and the capability of repeated and frequent measurements. Reproducibility of the measurements was demonstrated in three normal calves with a relative standard deviation of 3.9 +/- 2.4%. CBV was measured in eight calves with the Cleveland Clinic-Nimbus TAH and compared with that of seven calves that underwent mitral valve replacement. Small standard deviations in pre operative values in both TAH and mitral valve replacement groups demonstrated the precision of CBV measurements. Although there was no change in CBV in the mitral valve replacement group, CBV in the TAH group increased to more than twice the pre operative value after 2 weeks. Although the right atrial pressure increased similarly after TAH implantation, there was no correlation (r = 0.08) between the right atrial pressure and CBV, which suggested a possible inaccuracy in estimating CBV from the right atrial pressure. A negative correlation between the hematocrit value and CBV suggested that hemodilution might be one of the causes of anemia observed in our TAH animals.

Heat Dissipation from Artificial Hearts: Characterizing Tissue Responses and Defining Safe Levels

Mechanical artificial hearts generate heat, imposing unprecedented biomedical problems. Experiments were conducted in calves to study the effects of chronic heating and the mechanisms of the adaptation response, and to determine the safe levels for device-tissue interfacial temperatures. Electric heat sources which dissipated three different levels of constant heat flux (0.04, 0.06, or 0.08 W/cm2) were implanted adjacent to lung and muscle for up to seven weeks. The tissue temperatures were continuously monitored at the heater surface and 1, 3, and 7 mm from the surface. Correlating the local tissue temperatures with histologic features, the safe upper limit was identified to be 43°C, or 4°C above the body temperature. There were significant differences in tissue temperatures between the lung and muscle at all distances and with all three fluxes (P = 0.0001), reflecting a higher blood perfusion in the lung tissue. With the highest heat flux of 0.08 W/cm2, and the resultant initial surface temperature of 42.8°C ± 0.9°C, the lung showed no sign of tissue damage or necrosis, while the muscle, with a surface temperature of 45.3°C ± 2.2°C, was necrotic to a distance of 18.1mm and 3.0mm from the surface at 2 and 4 weeks, respectively. By the seventh week this muscle necrosis was totally replaced by fibrosis. Gradual decreases in the surface temperatures with the two higher heat fluxes and enhanced angiogenesis have suggested that the tissues adapt to chronic heating by increased perfusion. The expression of heat shock proteins by the tissue repair cells in the tissue capsule also suggests that cellular adaptation to heating is occurring.

ANALYSIS OF SUBCUTANEOUS FLUID IN RATS

Subcutaneous implantation in rats is a commonly used model for biomaterial calcification studies. Although this model is frequently used, its components have not been characterized with respect to calcification. Exudate from the subcutaneous spaces of 18 young rats was collected using diffusion chambers. These chambers consisted of polymethylmethacrylate tubes with 0.22 μ pore filters covering each end allowing fluid, but not cells, to enter the chambers. Glutaraldehyde treated bovine pericardial strips were implanted subcutaneously, inside the chambers and outside the chambers, to test the calcification inducing abilities of the various environments. The animals were killed on postoperative day 10, and the exudate and materials were collected. The exudate was analyzed for ionic calcium, total calcium, inorganic phosphorus, and albumin, and for cells by a differentiated cell smear. The materials were analyzed for calcification by radiography, histology, and atomic absorption. Calcification was present in the materials inside the chambers where no cells were present and in the materials that were not in chambers. The distinct features of the exudate were elevated ionic calcium, a high Ca X P product, and elevated phosphorus. ASAIO Journal 1997; 43:M405-M408.